Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men

Objectives. The aim of this study was to determine whether the combination of lipid-lowering therapy and vitamin E supplementation improves peripheral endothelial function and whether it is more effective than lipid-lowering therapy alone. Background. Endothelium-dependent vasodilation is impaired in coronary and peripheral arteries of patients with hypercholesterolemia. Coronary endothelial function has been shown to improve under lipid-lowering and antioxidant therapy, but the effect of additive vitamin E supplementation in the brachial artery is unknown. Methods. Seven patients with hypercholesterolemi (mean ± SD; age 51 ± 10 yr) were studied. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent nitroglycerin-induced dilation (NMD) were assessed in the brachial artery using high resolution ultrasound 1) at baseline (BL I), 2) after 8 weeks of simvastatin (20 mg) and vitamin E (300 IU) therapy (Comb I), 3) after withdrawal of vitamin E for 4 weeks (Statin), 4) after therapy as in #2 for 4 weeks (Comb II) and 5) after withdrawal of both drugs for 4 weeks (BL II). Results. Combined simvastatin and vitamin E therapy reduced total cholesterol (Comb I vs. BL I: 276 ± 22 vs. 190 ± 14 mg/dl, p < 0.0001) and low-density lipoprotein (LDL)-C (197 ± 22 vs. 106 ± 22 mg/dl, p < 0.00001), augmented alph tocopherol levels normalized to LDL (12.2 ± 4.1 vs. 4.9 ± 0.9 μg alpha-T/100 mg% LDL-C, p < 0.01) and resulted in significant improvements in FMD (16.4 ± 4.7 vs. 4.9 ± 2.5%, p < 0.001) as well as NMD (17.9 ± 4.3 vs. 11.2 ± 2.8%, p < 0.01). The ratio of FMD to NMD (0.92 ± 0.17 vs. 0.46 ± 0.24%, p < 0.05) also increased under combination therapy, indicating greater improvement of FMD than that of NMD. After withdrawal of vitamin E, both FMD (Comb I vs. Statin: 16.4 ± 4.7 vs. 7.9 ± 4.7%, p < 0.01) and NMD (17.9 ± 4.3 vs. 10.9 ± 4.5%, p < 0.05) decreased significantly such that simvastatin alone only tended to improve FMD and did not change NMD. Results under combination therapy (Comb II vs. BL II) were reproducible. Conclusions. Combined vitamin E and simvastatin therapy leads to an improvement of FMD and NMD in the brachial artery of patients with hypercholesterolemia. The improvement of FMD is more pronounced after combination therapy than after lipid-lowering therapy alone, similar to previous findings in the coronary circulation.